This invention relates to an article of manufacture comprising electrospun fibers. More particularly, this invention relates to composite nanofibers that can be produced by electrospinning polymeric matrix material. Even more particularly, this invention relates to a non-woven nanofiber composite that possesses improved qualities regarding strength, absorbency, and pH adjustability. This invention also relates to an apparatus for electrospinning the fibers. The apparatus of the present invention allows for the application of fibers to a specific target. The apparatus also allows for the application of fibers containing a wider range of potential performance enhancing additives than was previously believed possible.
The technique of electrospinning, also known within the fiber forming industry as electrostatic spinning, of liquids and/or solutions capable of forming fibers, is well known and has been described in a number of patents as well as in the general literature.
The process of electrospinning generally involves the creation of an electrical field at the surface of a liquid. The resulting electrical forces create a jet of liquid which carries electrical charge. Thus, the liquid jets maybe attracted to other electrically charged objects at a suitable electrical potential. As the jet of liquid elongates and travels, it will harden and dry. The hardening and drying of the elongated jet of liquid may be caused by cooling of the liquid, i.e., where the liquid is normally a solid at room temperature; evaporation of a solvent, e.g., by dehydration, (physically induced hardening); or by a curing mechanism (chemically induced hardening). The produced fibers are collected on a suitably located, oppositely charged receiver and subsequently removed from it as needed, or directly applied to an oppositely charged generalized target area.
Fibers produced by this process have been used in a wide variety of applications, and are known, from U.S. Pat. Nos. 4,043,331 and 4,878,908, to be particularly useful in forming non-woven mats suitable for use in wound dressings. One of the major advantages of using electrospun fibers in wound dressings, is that very thin fibers can be produced having diameters, usually on the order of about 50 nanometers to about 25 microns, and more preferably, on the order of about 50 nanometers to about 5 microns. These fibers can be collected and formed into non-woven mats of any desired shape and thickness. It will be appreciated that, because of the very small diameter of the fibers, a mat with very small interstices and high surface area per unit mass, two characteristics that are important in determining the porosity of the mat, can be produced.
Wound dressings formed using non-woven mats of these polymeric fibers may provide particular benefits depending upon the type of polymer or polymers used. A wettable, or hydrophilic, polymer, such as, for example, a polyurethane may be used, or a non-wetting, or at least weakly hydrophobic, polymer such as, for example, a saturated polyester, may be employed. Where the dressing is formed from a wettable polymer, blood or serum escaping from the wound tends to penetrate the dressing and the high surface area encourages clotting. Such dressings could be used as emergency dressings to halt bleeding. On the other hand, where the dressing is formed from a non-wetting polymer, and if the interstices between the fibers are sufficiently small, i.e., on the order of less than about 100 microns, tissue fluids, including blood, tend not to permeate the dressing. Consequently, the fluids are retained adjacent to the wound where clotting will occur. Subsequent removal of such a dressing is facilitated by the absence of blood clots permeating the dressing material. Still further, U.S. Pat. Nos. 4,043,331 and 4,878,908 suggest that such dressings have the advantage that they are usually sufficiently porous to allow interchange of oxygen and water vapor between the atmosphere and the surface of the wound.
Besides providing variability as to the diameter of the fibers or the shape, thickness, or porosity of any non-woven mat produced therefrom, the ability to electrospin the fibers also allows for variability in the composition of the fibers, their density of deposition and their inherent strength. The above-identified U.S. patents indicate that it is also possible to post-treat the non-woven mats with other materials to modify their properties. For example, one could increase the strength of the mat using an appropriate binder or increase water resistance by post-treating the mat with silicone or other water-resistant material.
By varying the composition of the fibers being electrospun, it will be appreciated that fibers having different physical or chemical properties may be obtained. This can be accomplished either by spinning a liquid containing a plurality of components, each of which may contribute a desired characteristic to the finished product, or by simultaneously spinning, from multiple liquid sources, fibers of different compositions that are then simultaneously deposited to form a mat. The resulting mat, of course, would consist of intimately intermingled fibers of different material. A further alternative noted in the U.S. patents is to produce a mat having a plurality of layers of different fibers of different materials (or fibers of the same material but different characteristics, e.g. diameter), as by, for example, varying the type of fibers being deposited on the receiver over time. For example, wettable and non-wetting polymers each offer additional properties that may be desirable in different applications. Wettable polymers tend to be highly absorbant but are relatively weak, while non-wetting polymers tend to be non-absorbant but relatively strong. In some applications, such as medical dressings, for example, it may be desirable to use a combination of wettable and non-wetting polymer layers in a single article. In such an application, the wettable polymer layer or layers contribute a relatively high level of absorbency to the article while the non-wetting polymer layer or layers contribute a relatively high level of strength. Use of such a laminate-type structure, however, suffers from the disadvantage that the hydrophobic layer can form a barrier to liquids and interfere with the absorption of liquid by the wettable layer. Additionally, upon absorption of liquid, the wettable polymer layer will lose its three dimensional structure, and misalignment, slipping, or even separation of the layers may occur, resulting in failure of the integrity of the article.
Thus, U.S. Pat. Nos. 4,043,331 and 4,878,908 make it clear that strong, non- woven mats comprising a plurality of fibers of organic, namely polymeric, material produced by electrostatically spinning the fibers from a liquid consisting of the material or precursor thereof is known in the art. These fibers are collected on a suitably charged receiver and subsequently removed therefrom. The mats or linings then formed on the receiver can then be transferred and used in conjunction with other previously constructed components such as, for example, mats of woven fibers and backing layers to provide a wound dressing of desired characteristics. For instance, in producing wound dressings, additional supports or reinforcement such as mats or linings of woven fibers, or backing layers are required in order to adhere the wound dressing to the skin and to provide other desirable properties to the wound dressing. As an example, a mat or lining of woven fibers may contain materials having antiseptic or wound-healing properties. Surface treatments of the already formed non-woven mats may also provide added benefits in the production of such wound dressings.
It has also been described in PCT Application No. WO 98/03267 to electrostatically spin a wound dressing in place over a wound. In such a use, the body itself is grounded and acts as a collector of the electrospun fibers. This method of synthesizing a wound dressing allows for solution of some of the problems associated with bandage and gauze storage and preparation. It is well known for example, that gauze and bandages must be stored and maintained in a sterile environment in order to offer the greatest protection in healing wounds. If the gauze or bandages are not sterile, these products offer little help in protecting the wound. Electrospinning a wound dressing in place, over a wound, from a sterile liquid, eliminates these problems.
Electrospinning a wound dressing in place over a wound, however, limits the types of solvents that may be used to only those solvents that are compatible with the skin or other tissue to which the dressing is applied. Examples of such solvents include water, alcohols, and acetone. Likewise, because the types of usable solvents are limited, the types of additives, such as, for example, absorbants, bacteriocides, and antibiotics, that may be used in conjunction with the polymer are also limited to those that are soluble in the particular solvent used. Similarly, the types of polymers that may be used are also limited to those that are soluble in a skin- or tissue- compatible solvent. Biocompatible polymer/solvent combinations include, for example, poly(ethylenimine)/ethanol, poly(vinylpyrrolidone)/ethanol, polyethylene oxide/water, and poly(2-hydroxymethacrylate)/ethanol+acid. While fibers from such a combination are non-reactive in their state as spun, exposure of the fibers to fluids, either from a wound or from external sources, may cause a local pH change from a neutral or nearly neutral pH to one that is acidic or alkaline, depending on the composition of the fiber. For example, when poly(ethylenimine) fiber is exposed to fluid, it will participate in proton transfer, resulting in an alkaline pH in the fluid contacting the polymer. The creation of an undesirable pH environment may cause side effects, such as slow wound healing.
As mentioned above, electrospinning involves the creation of a jet of fluid in an electrical field. The jet of fluid elongates and hardens or drys as it travels toward its target. The resulting fibers are deposited in a random and diffuse manner. This results in material being deposited outside the target area, causing waste. The general electric field on which formation of fibers depends, may also preclude deposition of fibers in the deepest part of a laceration or other deep wound, because fibers will be attracted to and deposit themselves on the portion of the wound closest to the electrospinning apparatus. The rate of hardening or drying is also dependent on factors such as the path length of the jet of fluid. This, in turn, influences the physical characteristics of the non-woven article.
Therefore, the need continues to exist for a wound dressing or other non-woven mat or membrane that is both strong and fluid absorbant. The need also exists for a wound dressing or other non-woven mat or membrane that is electrospun from biocompatible polymers and does not create an undesirable pH environment in the area of the polymer. The dressing or other non-woven mat should, however, still maintain all of the advantages provided in electrospinning the fiber(s) forming the dressing. There is also a need for a method of, and apparatus for, electrospinning a medical dressing or other non-woven mat or membrane that focuses the resulting fibers onto a specified target area. There is also a need for a method of, and apparatus for, the electrospinning of nanofibers which contain additives, without regard to their solubility in a biocompatible solvent/polymer combination. Likewise, there is also a need for a method of manipulating the rate of hardening of the electrospun fibers, and thereby manipulating the properties of the non- woven mat or membrane which is comprised of the electrospun fibers.
It is, therefore, an object of the present invention to provide electrospun fibers which are both strong and fluid absorbent.
It is another object of the present invention to provide an improved medical dressing for the treatment of a wound or other area of a patient requiring protection from contamination, comprising fibers which are both strong and fluid absorbent and optionally contain a pH adjusting component.
It is another object of the present invention to provide an improved medical dressing, as above, wherein the fibers of the dressing are electrospun.
It is still another object of the present invention to provide an improved medical dressing, as above, which may be applied to the wound by electrospinning in a more deliberately focused manner than previously known in the art.
It is still another object of the present invention to provide an improved medical dressing, as above, which can be readily applied to cover wounds having a wide range of sizes and shapes.
It is yet another object of the present invention to provide an improved medical dressing, as above, wherein the fibers forming the dressing are directly applied to a wound.
It is a further object of the present invention to provide an improved method for treating a wound of a patient.
It is still a further object of the present invention to provide a method for treating a wound, as above, wherein the fibers forming the wound dressing are directly applied to the wound.
It is yet a further object of the present invention to provide a method for treating a wound, as above, wherein the dressing is easily removable and is applied in a less painful manner than other traditional wound dressings.
It is still another object of the present invention to provide a single device for electrospinning composite polymer fibers and applying the composite polymer fibers to a wound surface.
At least one or more of the foregoing objects, together with the advantages thereof over the known art relating to electrostatic fiber spinning and wound dressings, which shall become apparent from the specification that follows, are accomplished by the invention as hereinafter described and claimed.
In general, the article of the present invention provides at least one fiber that has been formed by electrospinning a substantially homogeneous mixture of a polymer which is at least weakly hydrophobic, a hydrophilic polymer, and optionally, a pH adjusting component. Generally, at least weakly hydrophobic polymer fibers are fibers with an equilibrium moisture content of less than about 50 percent. Hydrophilic polymer fibers are fibers with an equilibrium moisture content of greater than about 60 percent. Polymer fibers with an equilibrium moisture content of greater than or equal to about 80 percent are generally considered hydrogels.
The article of the present invention also provides a fibrous matrix membrane comprising at least one fiber that has been electrospun as described hereinabove. This aspect of the present invention may take the form of a medical dressing. The article of the present invention may also be applied directly onto the three-dimensional topography of a wound to form the a medical dressing. The at least one fiber of this aspect of the present invention comprises a substantially homogeneous mixture of: a polymer which is at least weakly hydrophobic, a hydrophilic polymer, and optionally, a pH adjusting component. The article of the present invention may also optionally comprise one or more therapeutical performance enhancing compounds, including, for example, antibiotic compounds bacteriocidal compounds, fungicidal compounds, bacteriostatic compounds, crosslinking compounds, analgesic compounds, thrombogenic compounds, nitric oxide releasing compounds such as sydnonimines and NO-complexes that promote wound healing, other pharmaceutical compounds, adhesives, fragrances, odor absorbing compounds, and nucleic acids, without regard to solubility in a biocompatible solvent. In contrast to previous electrospun fibers, the additives are not limited to those that are soluble in the polymer/solvent combination. It has been discovered that even insoluble additives may be added to the polymer/solvent combination of the present invention without separation or segregation of the additive from the polymer in the electrospun fibers. Therefore, the term fluid, when used herein to describe the polymer/solvent combination of the present invention, is to be understood to include suspensions of particles that are insoluble in a given solvent.
Another aspect of the present invention is a method of making at least one fiber comprising electrospinning a substantially homogeneous mixture of: a solvent, a polymer which is at least weakly hydrophobic, a hydrophilic polymer, and optionally, a pH adjusting component.
Another aspect of the present invention is a method of making a fibrous matrix membrane comprising electrospinning a substantially homogeneous mixture of: a solvent, a polymer which is at least weakly hydrophobic, a hydrophilic polymer, and optionally, a pH adjusting component.
Another aspect of the present invention is a method of making a medical dressing whereby fibers are electrospun from a substantially homogeneous mixture comprising: a solvent, a polymer which is at least weakly hydrophobic, a hydrophilic polymer, and optionally, a pH adjusting component, with the resulting fibers being deposited on a suitably charged collection area and removed for subsequent usage.
In another aspect of the invention, the fibers are electrospun as described above and are deposited directly on its intended usage area without first applying the fibers to a transient, charged receiver or subjecting it to other intermediate fabrication steps. When the fibers are applied directly to a wound, the dressing can be made to accommodate any size or shape of wound. According to this aspect of the invention, the fibers are electrospun from a substantially homogeneous mixture of: a solvent, a polymer which is at least weakly hydrophobic, a hydrophilic polymer, and optionally, a pH adjusting component. Further, according to this aspect of the invention, when the fibers are electrospun directly onto a wound surface, the polymeric materials from which the fibers are electrospun are dissolved or suspended in a biocompatible solvent. Also according to this aspect of the invention, the initial polymeric liquid or solution employed may additionally comprise one or more pharmaceutical or therapeutical additives. The additives are not limited to those that are soluble in the biocompatible solvent or polymer/solvent combination. It has been discovered that even insoluble particulate additives may be dispersed in the polymer/solvent combination of the present invention without resulting in separation or segregation of the additive from the polymer in the electrospun fibers.
The method of making a medical dressing of the present invention also provides a method whereby the medical dressing is applied directly onto the three-dimensional topography of the wound to form the a medical dressing. According to this aspect of the present invention, fibers are electrospun from a mixture of: a solvent, a polymer which is at least weakly hydrophobic, a hydrophilic polymer, and optionally, a pH adjusting component. According to this aspect of the present invention, the electrospun fibers are focused onto a target area rather than being widely dispersed as previously known for electrospun fibers.
The present invention further provides a method of using a medical dressing comprising electrospinning one or more fibers to form a fibrous matrix membrane suitable for covering the wound. The fibers of the membrane are either directly assembled to the wound or first applied to a transient, charged receiver and/or subjected to other intermediate fabrication steps. The electrospun fibers in the method of the present invention comprise fibers which are a composite of: a polymer that is at least weakly hydrophobic, a hydrophilic polymer, and optionally a pH adjusting component. According to this aspect of the present invention, the fibers may also optionally comprise one or more therapeutic performance enhancing compounds, including, for example, antibiotic compounds, bacteriocidal compounds, fungicidal compounds, bacteriostatic compounds, crosslinking compounds, analgesic compounds, other pharmaceutical compounds, adhesives, fragrances, odor absorbing compounds, and nucleic acids. These compounds are applied to the treatment area via the wound dressing. The additives that may be applied to a wound via this aspect of the invention are not limited to those that are soluble in the polymer/solvent combination. It has been discovered that even insoluble additives may be added to the polymer/solvent combination of the present invention without separation or segregation of the additive from the polymer in the electrospun fibers. Therefore, the term fluid, when used herein to describe the polymer/solvent combination of the present invention, is to be understood to include suspensions containing particles that are insoluble in a given solvent.
The present invention also provides an apparatus for synthesizing at least one polymer fiber, the apparatus comprising: at least one reservoir, at least one device for electrospinning at least one fiber, the at least one device being in fluid communication with the at least one reservoir; a mixing device for agitating the fluid within the reservoir; and a power source capable of generating an electric field in electrical communication with the at least one device.
In another aspect of the present invention, the apparatus comprises a housing containing at least one reservoir for containing a fluid, a device for electrospinning the fluid into at least one fiber, the device being in fluid communication with the reservoir; a power source capable of generating an electric field in electrical communication with the device; and an extension extending from the housing for spacing the electrospinning device from the injured area, and a means for focusing the electrospun fibers into a defined area; wherein the fibers comprise: a polymer that is at least weakly hydrophobic, a hydrophilic polymer, and optionally a pH adjusting component.
The present invention also provides an apparatus for directly applying and assembling a plurality of electrospun fibers to a three dimensional surface of a wound either with or without any intermediate fabrication steps such as use of a transient, charged receiver, the apparatus comprising: at least one device for electrospinning at least one fiber; at least one reservoir for containing a fluid from which the at least one fiber is electrospun, the reservoir being in fluid communication with the at least one device for electrospinning the at least one fiber; a mixing device for agitating the spinning material; a power source in electrical communication with the at least one device for electrostatically spinning the at least one fiber; and a means for focusing the electrospun fibers into a defined area.
In one aspect of the present invention, the apparatus may further include a housing for encasing the other recited components of the apparatus and one or more legs or extensions connected to the housing for supporting the apparatus and/or for maintaining optimal spacing from the surface of the wound during use. The apparatus may use the patient""s body to attract the electrically charged fibers and, therefore, it is noted that the grounded electrical terminal of the apparatus may be connected to the patient by a separate wire or the like in a manner known in the art in order to aid in attracting or assembling the plurality of fibers onto the wound surface.